Experience of a District General Hospital With a Diverse Community in Operated Colorectal Cancers According to Ethnic Background

Background This study aimed to investigate disparities in colorectal cancer (CRC) patients’ demographics according to the five major ethnicities of patients living in the catchment area of North Middlesex Hospital. Methodology This retrospective study included CRC patients operated on between January 1, 2010, and December 31, 2014. Records dating to the end of the five-year follow-up were extracted anonymously from a database of CRC outcomes at the North Middlesex University Hospital NHS Trust. Comparisons were made according to ethnicity, patient demographics, type of presentation, cancer location, stage at diagnosis, recurrence, and mortality. Results A total of 176 adult patients were operated on for CRC between January 1, 2010, and December 31, 2014. The majority of the patients were referred as two-week wait target referrals. Emergency presentation of CRC was the highest in White non-UK patients. The White British Irish patients had their tumors mostly in the cecum, followed by the sigmoid colon, while the rectum followed by the sigmoid colon were the most common sites in the Black population. All study populations mainly presented with stage I disease, and the next highest incidence of cancers according to stage and ethnicity was stage IIIb in the Black population. Conclusions Differences in the ethnic background are important factors, especially in a diverse community, which can impact the age and mode of presentation of the disease, as well as the stage it starts to present. The location of the primary tumor, metastases, and recurrence sites are all affected by the ethnic background, which, subsequently, affect the survival of the patient.


Introduction
Cancer of the colon is the world's third most common cancer in males and the second most common cancer in females [1]. Colorectal cancer (CRC) will affect one in every 22 men and one in every 24 women in their lifetime [2]. Furthermore, 60% of cancers occur in developed countries [1]. Incidence rates are considerably higher in men than in women, with a sex ratio of 1.4:1. The incidence of CRC varies by more than a factor of 10 globally [3]. Australia and New Zealand have the highest incidence rates, with estimated agestandardized rates of 44.8 per 100,000 men and 32.2 per 100,000 women, with Europe and North America following closely. The lowest rates are seen in Africa at approximately 3.5 per 100,000 men and 3.0 per 100,000 women in Western Africa [3][4][5].
In the United Kingdom, access to medical care should not be affected by race or ethnic background. The Race Relations (Amendment) Act of 2000 emphasized the importance of ensuring racial equality of access to services [6].
Advanced age, male gender, a family background of colon or rectal cancer, a history of colorectal polyp, a history of inflammatory bowel disease, high body mass index (BMI), lack of physical activity, a history of type 2 diabetes, alcohol consumption, smoking, and a diet rich in red and processed meats are all linked with an increased risk of CRC [7][8][9]. However, increased calcium, fiber, folate, and vitamin D intake, as well     Figure 2).

FIGURE 2: Type of referral to the specialist service.
Regarding tumor location, the White British Irish population had their tumors mostly in the cecum, followed by the sigmoid colon, which was the same as the Asian population. However, the rectum followed by the sigmoid colon were the most common sites in the Black population. The White non-UK group had their cancers mostly in the sigmoid followed by the cecum (Figure 3).    The cancer stage at diagnosis showed that all study populations mainly presented with stage I disease. The next highest incidence of cancers according to stage and ethnicity was stage IIIb in the Black population ( Figure 4).

Discussion
While discussing the ethnic or racial background of CRCs, one has to bear in mind the difference between countries where similar studies were conducted discussing similar care topics. For example, in the United States, the key determinants of CRC screening include socioeconomic characteristics and physician supply. According to Soneji et al., adjusting for factors can explain the discrepancies between Black and White people regarding screening [18].
On comparing the incidence of CRC in the White population in the United States between 1992-1996 and 2010-2014, it was discovered that the rates increased from 7.5 to 11.0 per 100,000, whereas the incidence rate in the Black population increased from 11.7 to 12.7 per 100,000. Rectal cancer rates increased faster in Whites (from 2.7/100,000 to 4.5/100,000) than in Blacks (from 3.4/100,000 to 4.0/100,000) from 2010 to 2014. Rectal cancer rates were similar among Blacks and Whites [19]. In this study, rectosigmoid cancers (rectum + sigmoid colon) were more common in White non-UK and Black ethnicities than in White British Irish, whereas cecal cancers were more common in White British Irish compared to White non-UK and Black patients (RR = 1.637, CI = 1.090 to 2.457, p < 0.05) ( Table 4).
According to a recent systematic review [20], CRC is frequent in the White population in the United Kingdom, although it is uncommon among UK-based South Asians. In this study, only 10 Asian patients were operated on for CRC during the study period, which is about 5.6% of the total cancer operation load of the hospital. However, we did not study cancer incidence in the community per ethnicity as this study focused mainly on operated cancers from the time of diagnosis. known/suspected risk variables did not fully explain ethnic disparities in the age-adjusted incidence of CRC. Japanese Americans (both sexes) and African American women had a higher risk of CRC than Whites after accounting for differences in risk variable distribution [21].
In a heterogeneous, contemporary, population-based sample of 877,662 cancer patients in the United States, Ellis et al. [22] discovered continuing differences in survival for breast, prostate, lung, and colorectal cancer across racial/ethnic groups. Cancer-specific mortality was 36% higher in Black men (hazard ratio (HR) = 1.36, 95% CI = 1.30 to 1.43) and 34% higher in Black women in patients with CRC (HR = 1.34, 95% CI = 1.28 to 1.41). In this study, the five-year mortality of Black patients was 34%, with the highest mortalities occurring in the second year following cancer surgery. The five-year mortality of White non-UK patients was 38%, with the highest mortalities occurring in the third year of operation. Finally, in the White British Irish patients, the five-year mortality was 33%, with most deaths occurring in year one postoperatively ( Figure 5).
A retrospective, single-center investigation from Israel comprised 401 individuals with pathologically confirmed CRCs diagnosed between 2008 and 2015 [23]. These were split into two groups: Jewish (n = 334) and Arab (n = 67). The tumor stage, location, histologic grade, and mortality rate were collected and compared retrospectively between the two groups. Results showed that Arabs were significantly younger at diagnosis, which is comparable to the findings of this study in that there was an evident age discrepancy at the time of diagnosis between different ethnic groups. The White British Irish population had their cancers mainly in their ninth decade followed by the sixth decade with almost equal distribution between the seventh and eighth-decade cancers (Figure 1). Figure 1 also shows that other White non-UK patients had their cancers during their eighth, seventh, ninth, and sixth decades, implying that White populations tend to have CRCs later in life. However, in the Black population, CRCs occurred in the sixth, eighth, seventh, and ninth decades, implying that their CRCs presented earlier. There was a statistically significant finding that the White British Irish population developed cancers at a later age than Black patients with an RR of 1.905 (CI = 0.999 to 3.664, p < 0.05) ( Table 2).
Going back to the Israeli study, the tumor distribution through the colon was comparable between both groups and was characterized by a distal predominance. In the current study, the other ethnicity groups, which included Arabs, showed a similar outcome of distal tumors being more common than right colonic tumors. It appears that right-sided cancers are the most common in White and Asian populations. Furthermore, Black patients and other ethnicity groups had left-sided cancers more commonly than rightside cancers ( Table 3). Arabs had a much greater rate of the advanced stage upon diagnosis, according to the Israeli study, when compared to Jews, which adds evidence to the findings of this study regarding differences in presenting a stage of cancer based on ethnicity. As shown in Figure 4, White British Irish patients had their cancers at diagnosis mostly in stage I, followed by stage IIIb, while Black patients had stage I as the most common presenting stage, followed by stage IIb. Similarly, other White non-UK patients had stage I as the most common presentation. However, stages IIa and IIIa equally shared second place. Of note, Asian patients had 50% of the presentations as stage III.
In the study from Israel, the mortality rates of both groups were comparable. In this study, mortalities in the other ethnicity group reached 50% within five years of operation compared to White populations (33% and 38%) for the two White populations studied here ( Figure 5).
The increased prevalence of anal sexual practices among younger adults in Western countries, according to a study by Habel et al., may also be linked to the discrepancies in CRC frequencies among different ethnicities [24]. Anal intercourse may result in more contact between the anus and the rectum than vaginal intercourse due to lower condom use [25]. Sexually transmitted infections may have a role in CRC due to the close proximity of the rectum to the anus and the known carcinogenic association of human papillomavirus with anal cancer [26]. As human papillomavirus has a physiologic relationship with CRC, high-risk sexual behaviors among young adults can be a contributing factor [27].
Finally, it is well-recognized that inflammatory bowel disease and other causes of intestinal irritation increase the risk of CRC in White individuals. The mortality incidence rate for African Americans was 40.7%, which is the highest among races in the United States. Furthermore, Blacks have a CRC distribution that favors metastatic illness when compared to non-Hispanic Whites (NHWs). Black patients had a lower fiveyear survival rate than White patients, and their tumors had a higher proportion of Kirsten rat sarcoma (KRAS) gene mutations, making CRC more aggressive [28]. According to this study, the disparity in CRC in the United States, particularly between Blacks and NHWs, is likely multifactorial. It is uncertain if ensuring equal access to health care will be enough to overcome some of the biological factors that make CRC more aggressive in African Americans. In this study, Black patients presented with a high incidence of stage III and IV tumors (Figure 4), had a younger age at diagnosis (Figure 1), and had a high mortality rate of 34% within five years, which was the second following the other ethnicity group which showed 50% mortality but with a lower total number of patients (14 patients compared to 44 Black patients).
Tapan et al. [29] reported that overall survival was significantly lower in Black patients than in White patients, with a median overall survival of 1.9 and 2.5 years, respectively. Black race was found to be a significant risk factor for death in a multivariate analysis (HR = 1.7, CI = 1.01-2.9, p = 0.0467). Despite the assumption of equal access to health care and socioeconomic status within a safety-net hospital system, the findings of this study are consistent with previous research on CRC survival in Black patients and emphasize the importance of examining other risk factors such as genetic and pathogenic differences.
Furthermore, the type of initial referral to specialist service in this study was mostly the target type of referral in all ethnicity subtypes, while emergency referral was the second most common in White and Black populations with a significant increase in percentage in the Black population of about 22%.
The recurrence site was studied per population showing that the most common recurrence site in the White British Irish population was the liver, with 66.6% of recurrences, while 40% of the recurrences in the White non-UK patients were in the lungs. In Black patients, 50% of recurrences were in the lungs.
The limitations of this study include factors that may be related to ethnicity but are not genetically determined, such as socioeconomic status, ethnicity-related behaviors, or medical conditions, which can also predispose individuals to cancers as an indirect effect of ethnic background, thus likely impacting the outcome.
Further prospective studies should be conducted to confirm the effect of ethnicity on cancer progression and outcome.

Conclusions
CRCs are a major health challenge, and investigating their risk factors and pathogenic differences is a crucial aspect of management as it can modify the screening strategies and help tailor investigations and allocate resources accurately.
Differences in ethnic background are important factors, especially in a diverse community, which can impact the age and mode of presentation of the disease, as well as the stage it starts to present with. The location of the primary tumor, metastases, and recurrence sites are all affected by the ethnic background, which, subsequently, affects the survival of the patient.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.